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Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immun...
Source: Frontiers in Immunology - June 23, 2021 Category: Allergy & Immunology Source Type: research

Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
ConclusionsWe detected distinct anatomical and molecular changes in the stroke pathology between individual immunosuppressed mouse models that should be considered when selecting an appropriate mouse model for stroke research.
Source: Frontiers in Immunology - December 9, 2022 Category: Allergy & Immunology Source Type: research

Neutrophil Extracellular Trap Targeting Protects Against Ischemic Damage After Fibrin-Rich Thrombotic Stroke Despite Non-Reperfusion
Stroke is one of the most prevalent diseases worldwide caused primarily by a thrombotic vascular occlusion that leads to cell death. To date, t-PA (tissue-type plasminogen activator) is the only thrombolytic therapy approved which targets fibrin as the main component of ischemic stroke thrombi. However, due to its highly restrictive criteria, t-PA is only administrated to less than 10% of all stroke patients. Furthermore, the research in neuroprotective agents has been extensive with no translational results from medical research to clinical practice up to now. Since we first described the key role of NETs (Neutrophil Ext...
Source: Frontiers in Immunology - February 16, 2022 Category: Allergy & Immunology Source Type: research

The Role of Tenascin-C in Tissue Injury and Repair After Stroke
Stroke is still one of the most common causes for mortality and morbidity worldwide. Following acute stroke onset, biochemical and cellular changes induce further brain injury such as neuroinflammation, cell death, and blood-brain barrier disruption. Matricellular proteins are non-structural proteins induced by many stimuli and tissue damage including stroke induction, while its levels are generally low in a normal physiological condition in adult tissues. Currently, a matricellular protein tenascin-C (TNC) is considered to be an important inducer to promote neuroinflammatory cascades and the resultant pathology in stroke....
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Therapeutic Modulation of the Complement Cascade in Stroke
Stroke is a leading cause of death and disability worldwide and an increasing number of ischemic stroke patients are undergoing pharmacological and mechanical reperfusion. Both human and experimental models of reperfused ischemic stroke have implicated the complement cascade in secondary tissue injury. Most data point to the lectin and alternative pathways as key to activation, and C3a and C5a binding of their receptors as critical effectors of injury. During periods of thrombolysis use to treat stroke, acute experimental complement cascade blockade has been found to rescue tissue and improves functional outcome. Blockade ...
Source: Frontiers in Immunology - July 29, 2019 Category: Allergy & Immunology Source Type: research

Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke
Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration eithe...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Microglia autophagy in ischemic stroke: A double-edged sword
Ischemic stroke (IS) is one of the major types of cerebrovascular diseases causing neurological morbidity and mortality worldwide. In the pathophysiological process of IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation is characterized by the activation of microglia, and increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators and signaling pathways. In this paper, we summarized the beneficial and harmful effects of microglia in IS. In addition, we discussed the interplay ...
Source: Frontiers in Immunology - November 16, 2022 Category: Allergy & Immunology Source Type: research

Phagocytosis in the Brain: Homeostasis and Disease
Conclusions and Perspectives In this review we have summarized the critical role phagocytosis plays in both CNS homeostasis and disease. While much progress has been made in recent years, many unanswered questions remain. How phagocytosis in the CNS is influenced by numerous factors, such as microenvironment or phagocytic target, have yet to be fully resolved. Additionally, the utilization of novel technologies, including in vivo imaging techniques (217), iPSC-derived microglia (213) and high-throughput screens (66), will likely contribute to further identification of phagocytic pathways and consequences of phagocytosis w...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

New Insight Into Neutrophils: A Potential Therapeutic Target for Cerebral Ischemia
Ischemic stroke is one of the main issues threatening human health worldwide, and it is also the main cause of permanent disability in adults. Energy consumption and hypoxia after ischemic stroke leads to the death of nerve cells, activate resident glial cells, and promote the infiltration of peripheral immune cells into the brain, resulting in various immune-mediated effects and even contradictory effects. Immune cell infiltration can mediate neuronal apoptosis and aggravate ischemic injury, but it can also promote neuronal repair, differentiation and regeneration. The central nervous system (CNS), which is one of the mos...
Source: Frontiers in Immunology - July 14, 2021 Category: Allergy & Immunology Source Type: research

Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model
In this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used single-cell State Transition Across-samples of RNA-seq data (scSTAR), a new bioinformatics method, to analyze the single-cell transcriptional profile of day 1, 3, and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequences and proteomics data, we found the importance of the integrin beta 2 (Itgb2) gene in post-modeling. And microglia of Itgb2+ and Itgb2- were clustered by the scSTAR method. Finally, the functions of the subpopulations were defined by Matescape, and three different time po...
Source: Frontiers in Immunology - March 30, 2023 Category: Allergy & Immunology Source Type: research

Subclinical Atherosclerosis in Primary Sj ögren's Syndrome: Does Inflammation Matter?
Conclusions The markers of endothelial activation and damage and of chronic inflammation investigated until now failed to result predictors of subclinical atherosclerosis or to be associated with increased risk of CV events in SS patients. This may suggest that other mechanisms are implicated with increased prevalence of subclinical atherosclerosis in SS or that these biomarkers exert a different mechanism in the pathogenesis of endothelial damage and in the induction of atherosclerosis. Surely, the relationship between the disease itself and inflammatory and immune dysfunction factors is quite complex and still to be cla...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Effects of Normothermic Machine Perfusion Conditions on Mesenchymal Stromal Cells
In this study the effect of NMP perfusion fluid on survival, metabolism and function of thawed cryopreserved human (h)MSC and porcine (p)MSC in suspension conditions was studied. Suspension conditions reduced the viability of pMSC by 40% in both perfusion fluid and culture medium. Viability of hMSC was reduced by suspension conditions by 15% in perfusion fluid, whilst no differences were found in survival in culture medium. Under adherent conditions, survival of the cells was not affected by perfusion fluid. The perfusion fluid did not affect survival of fresh MSC in suspension compared to the control culture medium. The f...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Pentraxin 3 in Cardiovascular Disease
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

The intestinal γδ T cells: functions in the gut and in the distant organs
Located in the frontline against the largest population of microbiota, the intestinal mucosa of mammals has evolved to become an effective immune system. γδ T cells, a unique T cell subpopulation, are rare in circulation blood and lymphoid tissues, but rich in the intestinal mucosa, particularly in the epithelium. Via rapid production of cytokines and growth factors, intestinal γδ T cells are key contributors to epithelial homeostasis and immune surveillance of infection. Intriguingly, recent studies have revealed that the intestinal γδ T cells may play novel exciting functions ranging from epithelial plasticity and ...
Source: Frontiers in Immunology - June 16, 2023 Category: Allergy & Immunology Source Type: research